Boxed Warning
The most prominent safety warning in a drug's labelling, enclosed in a black border. The FDA requires boxed warnings for risks serious enough to warrant special consideration before prescribing. They alert healthcare professionals to potentially life-threatening adverse effects or critical use restrictions.
Technical Context
The FDA can require a boxed warning under 21 CFR 201.57(c)(1) when: a serious adverse reaction can be prevented or its severity reduced through appropriate use, a serious adverse reaction exists that limits the drug's use, or the drug has a specific population risk. Examples beyond GLP-1 RA C-cell warning: corticotropin (immunosuppression risk), cyclosporine systemic (nephrotoxicity, neoplasia, serious infections), and various oncology peptides. Boxed warnings must include: a brief summary of the risk, affected population, recommended monitoring or contraindications, and any REMS requirements. The decision to add, modify, or remove a boxed warning involves FDA internal review, may include advisory committee input, and considers: strength of evidence, severity of risk, ability to mitigate through labelling, and benefit-risk balance.